Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany.
Cancer Med. 2023 Feb;12(4):4655-4666. doi: 10.1002/cam4.5072. Epub 2022 Jul 26.
Whether and to what extent the relationship between physical activity (PA) and colorectal cancer (CRC) differs according to CRC-related genetic risk remains to be determined, and no studies to date have quantified how much genetically determined risk could be compensated for with active exercise.
Genetic risk was quantified by a polygenic risk score (PRS) summarizing the estimated effect of 140 CRC-associated genetic variants. Associations of PA with CRC risk were estimated by multivariable logistic regression across PRS levels. We also compared the impact of PA and specific PA types to the PRS using "genetic risk equivalent (GRE)", a novel approach to enhance effective risk communication.
Among 5058 CRC patients and 4134 controls, we observed no significant association between overall PA level in quartiles and CRC risk. However, the highest versus lowest lifetime leisure time physical activity (LTPA) was associated with a 13% lower CRC risk [odds ratio 0.87, 95% confidence interval (CI) 0.77-1.00] independent of PRS levels (adjusted p value for interaction = 0.18). This effect was equivalent to the effect of having 11 percentiles lower PRS (GRE -10.6, 95% CI -20.7 to -0.6). The GRE (95% CI) for the highest lifetime sports tertile was -23.0 (-33.9 to -12.0).
LTPA was inversely associated with CRC risk irrespective of polygenic risk for CRC, which reinforces the importance of LTPA in CRC prevention among the general population. Adequate sports activity can compensate for a large share of polygenic risk for CRC.
体力活动（PA）与结直肠癌（CRC）之间的关系是否以及在何种程度上因 CRC 相关的遗传风险而异仍有待确定，迄今为止尚无研究量化通过积极运动可以抵消多少由遗传决定的风险。
通过汇总 140 个 CRC 相关遗传变异的估计影响的多基因风险评分（PRS）来量化遗传风险。通过多变量逻辑回归在 PRS 水平上估计 PA 与 CRC 风险之间的关联。我们还使用“遗传风险等效（GRE）”比较了 PA 和特定 PA 类型对 PRS 的影响，这是一种增强有效风险沟通的新方法。
在 5058 名 CRC 患者和 4134 名对照中，我们没有观察到总体 PA 水平在四分位区间与 CRC 风险之间存在显著关联。然而，最高与最低终生休闲体力活动（LTPA）与 CRC 风险降低 13%相关[比值比 0.87，95%置信区间（CI）0.77-1.00]，独立于 PRS 水平（调整后的交互作用 p 值为 0.18）。这种效果相当于 PRS 降低 11 个百分位数的效果（GRE-10.6，95%CI-20.7 至-0.6）。最高终生运动三分位的 GRE（95%CI）为-23.0（-33.9 至-12.0）。
无论 CRC 的多基因风险如何，LTPA 与 CRC 风险呈负相关，这强化了 LTPA 在普通人群中预防 CRC 的重要性。足够的运动活动可以补偿 CRC 多基因风险的很大一部分。
